Mitochondrial decay due to oxidation is an important contributor to Parkinson's disease (PD) and other neurodegenerative diseases of aging. We have previously shown that mitochondrial decay in old rats can be ameliorated by feeding them the normal mitochondrial metabolites R-alpha-lipoic acid (LA) and acetyl-L-carnitine (ALCAR), which inhibited oxidative damage and restored much of the mitochondrial structure and function in old animals. There is evidence that some mitochondrial metabolites may protect against PD. For example, coenzyme Q10 (CoQ) has been shown to protect against PD in clinical trials in humans; and ALCAR has been shown to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity, a PD mimic in monkeys. These metabolites protect by restoring mitochondrial antioxidants and function. We hypothesize that a mixture of mitochondrial antioxidants/metabolites, CoQ, ALCAR and LA, could be optimized to be more effective than any single compound in preventing or treating PD. We will test our hypothesis using behavioral, biochemical, and immunohistochemical techniques on two models of PD: the chronic rotenone-exposed SK-N-MC human neuroblastoma cell model and the chronic rotenone-treated rat model. This project on PD is a new direction for our work on preventing mitochondrial decay and could lead to an effective and cost efficient prevention /therapy for PD.